The Herpes simplex virus (HSV) particle consists of a DNA-containing capsid surrounded by a lipid envelope which bears a diverse array of membrane proteins. Lining the inner surface of the envelope is a complex and poorly characterized layer of polypeptides termed tegument. The HSV envelope is acquired by budding of capsids through host cell organellar membranes, and envelope formation is essential for the subsequent transmission of viral disease. However, little is known of the molecular details of envelope assembly. A key step in envelope formation is likely to be the binding of tegument polypeptides to the cytoplasmic tails of viral envelope glycoproteins. This recruitment of tegument onto the membrane may then provide a binding site for the viral capsid. We have confirmed this hypothesis by developing assay systems which reconstitute the interaction of glycoprotein tails, tegument proteins and HSV capsids in vitro. With these assay systems available we now propose to use biochemical and recombinant DNA techniques to investigate the molecular events which take place during HSV particle assembly.